ArticleJournal of experimental & clinical cancer research : CR2022
CXCR4-targeted nanotoxins induce GSDME-dependent pyroptosis in head and neck squamous cell carcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Pharmacological Targeting of CXCR4 Attenuates Sepsis-Induced Intestinal Injury by Suppressing NLRP3/GSDMD-Mediated Pyroptosis.Inflammation · 2026Article
- USP7 overexpression prevents the progression of clear cell renal cell carcinoma by enhancing pyroptosis via TRIP12 deubiquitination.Cancer biology & therapy · 2025Article
- Phosphorylated IRF3 promotes GSDME-mediated pyroptosis through RIPK1/FADD/caspase-8 complex formation during mitotic arrest in ovarian cancer.Cell communication and signaling : CCS · 2025Article
- Targeting the chemokine receptor CXCR4 for cancer therapies.Biomarker research · 2025Review
- An optimized integrin α6-targeted peptide capable of delivering toxins for melanoma treatment.Journal of translational medicine · 2025Article
- Article
- Nanomaterial-Driven Regulated Cell Death: Mechanistic Insights and Novel Strategies for Tumor Therapy.International journal of nanomedicine · 2025Review
- A Targeted Nanotoxin Inhibits Colorectal Cancer Growth Through Local Tumor Pyroptosis and Eosinophil Infiltration and Degranulation.International journal of nanomedicine · 2025Article
- Bacterial exotoxins in medicine: potential value and perspectives.International journal of medical sciences · 2025Review
- Evaluation of pyroptosis-associated genes in endometrial cancer utilizing a 101-combination machine learning framework and multi-omics data.Frontiers in medicine · 2025Article
- The characteristics and functional significance of disulfidptosis-related genes in head and neck squamous cell carcinoma.Discover oncology · 2024Article
- Pyroptosis in health and disease: mechanisms, regulation and clinical perspective.Signal transduction and targeted therapy · 2024Review
- Nanomedicine-induced programmed cell death enhances tumor immunotherapy.Journal of advanced research · 2024Review
- Effect of radiotherapy on head and neck cancer tissues in patients receiving radiotherapy: a bioinformatics analysis-based study.Scientific reports · 2024Article
- Review
- Article
- Nanomaterials Enhance Pyroptosis-Based Tumor Immunotherapy.International journal of nanomedicine · 2024Review
- Cancer immunogenic cell death via pyroptosis with CXCR4-targeted nanotoxins in hepatocellular carcinoma.Frontiers in bioengineering and biotechnology · 2024Article
- The multifaceted roles of GSDME-mediated pyroptosis in cancer: therapeutic strategies and persisting obstacles.Cell death & disease · 2023Review
- The role of pyroptosis and gasdermin family in tumor progression and immune microenvironment.Experimental hematology & oncology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundTherapy resistance, which leads to the development of loco-regional relapses and distant metastases after treatment, constitutes one of the major problems that head and neck squamous cell carcinoma (HNSCC) patients currently face. Thus, novel therapeutic strategies are urgently needed. Targeted drug delivery to the chemokine receptor 4 (CXCR4) represents a promising approach for HNSCC management. In this context, we have developed the self-assembling protein nanotoxins T22-PE24-H6 and T22-DITOX-H6, which incorporate the de-immunized catalytic domain of Pseudomonas aeruginosa (PE24) exotoxin A and the diphtheria exotoxin (DITOX) domain, respectively. Both nanotoxins contain the T22 peptide ligand to specifically target CXCR4-overexpressing HNSCC cells. In this study, we evaluate the potential use of T22-PE24-H6 and T22-DITOX-H6 nanotoxins for the treatment of HNSCC.
methodsT22-PE24-H6 and T22-DITOX-H6 CXCR4-dependent cytotoxic effect was evaluated in vitro in two different HNSCC cell lines. Both nanotoxins cell death mechanisms were assessed in HNSCC cell lines by phase-contrast microscopy, AnnexinV/ propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and western blotting. Nanotoxins antitumor effect in vivo was studied in a CXCR4
resultsFirst, we found that both nanotoxins exhibit a potent CXCR4-dependent cytotoxic effect in vitro. Importantly, nanotoxin treatment triggered caspase-3/Gasdermin E (GSDME)-mediated pyroptosis. The activation of this alternative cell death pathway that differs from traditional apoptosis, becomes a promising strategy to bypass therapy resistance. In addition, T22-PE24-H6 and T22-DITOX-H6 displayed a potent antitumor effect in the absence of systemic toxicity in a CXCR4
conclusionsAltogether, our results show that T22-PE24-H6 and T22-DITOX-H6 represent a promising therapy for HNSCC patients. Remarkably, this is the first study showing that both nanotoxins are capable of activating caspase-3/GSDME-dependent pyroptosis, opening a novel avenue for HNSCC treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.